The tankyrase inhibitor G007-LK inhibits small intestine LGR5⁺ stem cell proliferation without altering tissue morphology.

ABSTRACT:

Background

The WNT pathway regulates intestinal stem cells and is frequently disrupted in intestinal adenomas. The pathway contains several potential biotargets for interference, including the poly-ADP ribosyltransferase enzymes tankyrase1 and 2. LGR5 is a known WNT pathway target gene and marker of intestinal stem cells. The LGR5⁺ stem cells are located in the crypt base and capable of regenerating all intestinal epithelial cell lineages.

Results

We treated Lgr5-EGFP-Ires-CreERT2;R26R-Confetti mice with the tankyrase inhibitor G007-LK for up to 3 weeks to assess the effect on duodenal stem cell homeostasis and on the integrity of intestinal epithelium. At the administered doses, G007-LK treatment inhibited WNT signalling in LGR5⁺ stem cells and reduced

SUBMITTER: Norum JH 

PROVIDER: S-EPMC5759193 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature